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Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui.


ABSTRACT: Cells harboring latent HIV-1 pose a major obstacle to eradication of the virus. The 'shock and kill' strategy has been broadly explored to purge the latent reservoir; however, none of the current latency-reversing agents (LRAs) can safely and effectively activate the latent virus in patients. In this study, we report an ingenol derivative called EK-16A, isolated from the traditional Chinese medicinal herb Euphorbia kansui, which displays great potential in reactivating latent HIV-1. A comparison of the doses used to measure the potency indicated EK-16A to be 200-fold more potent than prostratin in reactivating HIV-1 from latently infected cell lines. EK-16A also outperformed prostratin in ex vivo studies on cells from HIV-1-infected individuals, while maintaining minimal cytotoxicity effects on cell viability and T cell activation. Furthermore, EK-16A exhibited synergy with other LRAs in reactivating latent HIV-1. Mechanistic studies indicated EK-16A to be a PKC? activator, which promoted both HIV-1 transcription initiation by NF-?B and elongation by P-TEFb signal pathways. Further investigations aimed to add this compound to the therapeutic arsenal for HIV-1 eradication are in the pipeline.

SUBMITTER: Wang P 

PROVIDER: S-EPMC5573388 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui.

Wang Pengfei P   Lu Panpan P   Qu Xiying X   Shen Yinzhong Y   Zeng Hanxian H   Zhu Xiaoli X   Zhu Yuqi Y   Li Xian X   Wu Hao H   Xu Jianqing J   Lu Hongzhou H   Ma Zhongjun Z   Zhu Huanzhang H  

Scientific reports 20170825 1


Cells harboring latent HIV-1 pose a major obstacle to eradication of the virus. The 'shock and kill' strategy has been broadly explored to purge the latent reservoir; however, none of the current latency-reversing agents (LRAs) can safely and effectively activate the latent virus in patients. In this study, we report an ingenol derivative called EK-16A, isolated from the traditional Chinese medicinal herb Euphorbia kansui, which displays great potential in reactivating latent HIV-1. A comparison  ...[more]

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